Device for performing urease tests on combined antrum/corpus biopsies to diagnose gastrointestinal illnesses

ABSTRACT

A device for carrying out urease tests for combined antrum/corpus biopsies to diagnose gastro-intestinal illnesses has a carrier plate, a schematic representation of the stomach on the plate, at least one opening in the plate at the locations corresponding to the corpus and the antrum in the schematic representation of the stomach, an evaluation scale for assessment of the urease test and an area for data on the patient and for clinical data.

BACKGROUND OF THE INVENTION

1. Field of Invention

The invention concerns a device for conducting combined urease tests onantrum/corpus biopsies for diagnosis of gastrointestinal disorders.

2. Brief Description of the Related Art

Gastrointestinal disorders such as duodenal or gastric ulcers, andespecially chronic, active gastritis, are closely associated with thepartial or diffuse colonization of Heliobacter pylori (HP) in thestomach. HP, also known as Campylobacter pylori, is a bacterium whichcatabolizes urea. The general indicator of bacteria such as HP whichcatabolize urea was described by Stuart et al. (J. Bacteriol, 1945, 49,437) and Christensen (J. Bacterial. 1946, 52, 461). Regarding theabove-mentioned illnesses, HP is regarded as an established cause ofchronic Type B gastritis (Rauws et al., Gastroenterology 1988, 94, 33).In the case of an ulcer, HP represents a risk factor for predispositionof duodenal ulcer recurrence (Coghlan et al., Lancet II, 1987, 1109). Inrecent years, therefore, more and more reliable and, above all else,more practical indicator methods for HP have been sought. For reasons ofease of implementation and reduced cost-outlays, the analyses of biopsyprobes with urease tests have acquired increased significance as opposedto very sensitive and specific culture techniques.

A culture medium for differentiation of microorganisms which catabolizeurea was described by Christensen (J. Bacteriol. 1946, 52, 461) andbased on the breakdown of urea by microorganisms that contain urease.The decomposition of urea into carbon dioxide and ammonia leads to analkaline reaction in the medium, which is signalled when thecolor-indicator, phenol red, turns from yellow to red.

A modified quick-test which offers diagnostic advantages when thespecimen exhibits only a limited colonization of Heliobacter pylori wasdescribed by Malfertheiner (Acta Therapeutica, 1988, 14, 205).

According to Borsch et al. (Immun. Infekt. 1989, 17, 83-90) the combinedexamination of antrum and corpus biopsies generally affords a superiordiagnostic sensitivity and specificity for indication of the HPcolonization of the stomach when compared with a single biopsy.Additionally, the results are thoroughly comparable to that of the moresensitive culture techniques. The combination of two antral urease testsis definitely inferior to the combined examination through biopsies ofthe antrum and corpus. ccording to Borsch et al, the combined ureasetests of an antrum-corpus biopsy represent efficient diagnosticprocedure with regard to expense and results. Urease tests areparticularly the method of choice when the more sensitive, and generallymore costly, culture techniques are not available.

In EP-PS 204-438 a procedure for determining the presence of urease instomach material was described. This procedure used a combination ofurea, a bactericide which sharply hindered the growth of theurease-producing organism, and a pH-indicator, (for example, phenol red)in a chemical medium, essentially bacteriological agar. The device whichEP 204 438 illustrated in FIGS. 1 through 3 consists of a rectangularplate in which a small bowl fitted with a flexible covering can be usedto receive the agar described above. This device is commerciallyavailable as CLO-Test®.

The devices which have been previously described, and which aregenerally used for urease tests, essentially consist of simple,closeable containers which serve to receive either a corpus or an antrumbiopsy. These containers must be correspondingly marked or tediouslylabeled so that the biopsies are not confused. Because these containers(for example, Eppendorf tubes) are very small, it is not possible tolabel them with the important patient data, with clinical documentation,and/or with test times and results.

Through use of appropriate labels, a careful marking with the importantpatient data is usually avoided for economic reasons. In routinelaboratory operation, then, it can happen that biopsies which were takencould be falsely classified or biopsies of several patients could beconfused.

Devices which do not have these disadvantages and which allow thesimultaneous reception of the antrum and corpus biopsies for thecombined urease test of antrum/corpus biopsies have, up until now, notbeen available because of the current state of technology.

SUMMARY OF THE INVENTION

The task of this invention, therefore, is to provide a device whichallows the performance of combined antrum/corpus tests for diagnosis ofgastrointestinal disorders and which provides for those using the devicea distinctive classification of the biopsies taken of the antrum andcorpus. The goal of this invention is, particularly, to offer theexamining physician a simple, quick, and sure operation of the device,and to prevent the confusion of the biopsies of several patients.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a perspective view of a device for performing combined ureasetests on antrum and corpus biopsies according to the present invention.

FIG. 2A is a cross-section of the device of FIG. 1 taking along the line2--2 of FIG. 1 showing a foil covering in a partially installedposition.

FIG. 2B is a cross-section of the device of FIG. 1 taking along the line2--2 of FIG. 1 showing a foil completely covering the openings.

FIG. 3 is side section view of an alternate embodiment of the apparatusof Claim 1 showing the feature of rubber washers provided for holdingtubes.

FIG. 4 is a cross-sectional view of an alternate embodiment of thepresent invention showing a carrier plate with integral sample tubeshaving a rim protruding upwardly from the carrier plate.

FIG. 5 is a top plan view of a carrier plate according to the presentinvention, showing a preferred labelling scheme.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

A device has been invented which fulfills this task according to Claim#1. It is equipped with:

a) a carrier plate,

b) a schematic representation of the stomach on the carrier plate,

c) at least one opening in the aforementioned carrier plate

which corresponds to the corpus and antrum, respectively, in theschematic representation,

d) an evaluation scale for assessment of the urease tests, and

e) an area for patient data and clinical documentation.

In a model of the invention, the openings described above serve toreceive and to fix in place commonly used, closeable specimen containerswhich hold the medium used for the urease test. The schematicrepresentation of the stomach is either pressed or engraved onto thecarrier plate of this model.

A particularly preferred device is one in which the openings describedabove are openings of containers which are permanently connected to thecarrier plate, these containers holding a culture medium for the ureasetest being performed and having a sealable lid. A cover which is securedto the carrier plate is the preferred sealing device. An adhesive sealin the form of transparent foil, for example, can serve as an alternate.If such an adhesive seal is used, it can be imprinted with the schematicrepresentation of the stomach. In this way the schematic representationis applied to the carrier plate not through printing or engraving, butwith the printed foil. The openings in the carrier plate can be sealedeither with separate pieces of foil or by a single foil piece. It ispreferable to use only a single foil to seal the openings. Mostpreferable is for the schematic representation of the stomach to beprinted or engraved directly on the carrier plate and the openingssealed with a cover or with transparent, unprinted foil. In this way,proper classification of the antrum and/or corpus biopsies is guaranteedeven if the adhesive seal is completely removed.

In a later model the carrier plate contains more than one opening in theareas corresponding to the corpus and to the antrum. This offers theadvantage of allowing several simultaneous antrum/corpus biopsies forthe combined antrum/corpus urease test. With the additional comparisonbiopsies allowed through use of this same carrier plate, the risk offalse-positives on the urease tests is significantly reduced.

The device which was invented can be used in combination with the ureasetests which are commonly used. A gel-like substrata is generally usedcontaining per 1,000 g: 0.1 g yeast extract, 0.1 g potassium dihydrogenphosphate, 0.6 g phenol red, 14.4 g agar, 0.1 g dextrose, 19.2 g urea,2.9 ml vitamin solution, and 0.1 ml solution of trace elements.

The vitamin solution referred to is prepared by dissolving 0.198 g D (+)vitamin H, 1.977 g niacin, 0.988 g vitamin B₁, 0.988 g paraaminobenezyne carboxylic acid, 0.494 g deuterium pantothenic acid-sodiumsalt, 4.942 g Pyridoxamine dihydrochloride, and 1.977 g vitamin B₁₂ in988.435 g of distilled water with sterile filtration following. Thesolution of trace elements referred to is prepared by dissolving 0.049 gof barium chloride--2 H₂ O, 0.198 g neutral potassium iodide, 0.198 gpotassium bromide, 0.099 g boric acid, 0.049 g tin chloride, 0.049 glithium chloride, 0.198 g zinc chloride--2 H₂ O, 0.099 g copper (II)sulfate--5 H₂ O, 0.198 g cobalt chloride--6 H₂ O, 0.99 g manganesedichloride--4 H₂ O, 7.919 g Titriplex® III 2 H₂ O, 0.01 g iron (II)sulfate--7 H₂ O, and 0.099 sodium molybdate--H₂ O in 989.844 g distilledwater with sterile filtration following. Pure substances and/orsubstances for the performance of the analysis (yearly) are chieflyused.

The basic preparation, containing no urea, is autoclaved and mixed withthe thermolabile components at a temperature of less than 62° C. toproduce the ready-to-use preparation. The pH factor of the substrate isadjusted to 6.0±0.1.

The device we have invented provides an easily operated aid toestablishing a diagnosis of gastrointestinal illnesses by allowing thesensitive and specialized combination urease tests for antrum/corpusbiopsies to be performed. The schematic representation of the stomach onthe carrier plate with containers in the areas of the corpus and antrum,as schematically represented, ensures a simple classification of thesample and thereby reduces the possible confusion of the biopsies takenfrom the antrum and corpus. The device is easily operated in all casesand, because the patient data relating not only to the antrum, but alsoto the corpus, as well as clinical data such as test time and results,is found on a single carrier near the biopsy, possible confusion orexchanges are avoided. The evaluation scale found on the carrier plateallows for a rapid and clear determination of diagnosis through a directcomparison of color changes which occur in the side-by-side culturemedia containing the antrum and corpus biopsies. The biopsies remaintogether on the carrier plate and can also be compared after 24 hrs. toany color changes in the urease tests.

The form of the device permits an advantageous storing of the specimens.

The invention is described in the following through use of examples:

EXAMPLE 1

FIG. 1 shows a device for performing combined urease tests on antrum andcorpus biopsies for diagnosis of gastrointestinal illnesses. A schematicrepresentation of the stomach (2) is found on the carrier plate (1). Oneach of the places corresponding to the antrum and to the corpus, anopening (3) is located. An evaluation scale (4) for assessment of thetest results, preferably with colored markings, is located on thecarrier plate (1). The first field (5) which is found on the carrierplate collects patient data and clinical documentation. That is, thefinal assessment of the combined urease tests of an antrum/corpus biopsycan be entered here. The second field (6) contains further informationon the combined urease test, such as manufacturer or general comments.

EXAMPLE 2

FIG. 2 shows a cross-section of a device corresponding to FIG. 1 for theperformance of combined urease tests on antrum/corpus biopsies fordiagnosis of gastrointestinal illnesses. During these tests the carrierplate (1) in the device portrayed in FIG. 1 has a container (14) whichis filled with substratum (13). This container (14) is sealed with thehelp of a foil (16). The location of the container (14) in FIG. 2 isidentical to the opening (3) in FIG. 1.

EXAMPLE 3

The device represented in FIG. 1 serves to receive the sealablecontainers or tubes which contain the substratum used for the ureasetests.

FIG. 3 shows a cross-section of a device for the performance of combinedurease tests on antrum/corpus biopsies for diagnosis of gastrointestinalillnesses, during which the tubes mentioned are placed in the openings(8) in the carrier plate (1'). The tubes are then fixed in place withthe help of rubber washers and/or rings (7) installed in the openings.The position of the openings (10) in FIG. 4 corresponds to the positionof the openings (3) in FIG. 1 and provides for a clear alignment toeither corpus or antrum.

EXAMPLE 4

FIG. 4 shows a cross-section of a device which combines the featuresfound in the alternatives discussed in Examples 2 and 3. The container(14) which fits into the carrier plate (1) in FIG. 2 is provided with arim (15) (FIG. 4) that protrudes above the level of the carrier plate(1") which virtually leads to the opening or tubes (10) that areintegrated into the carrier plate (1") in FIG. 4. The rim (15) of thecontainer (10) that stands above the plane of the carrier plate (1")allows a sealing device, for example, a cover in the form of a sealingstopper (11) (FIG. 4), to be attached. Another preferred closure is ascrew-on cap with cylindrical in-lays which forces inner contact of thebiopsy with the substratum used for the urease test by pushing thebiopsy down into the substratum. The substratum (12) used in the ureasetest can be put into this container (10). The container (10) (FIG. 4)lies in the region of the openings (3) represented in FIG. 1 and allowsfor classification of corpus and antrum.

EXAMPLE 5

FIG. 5 shows an overview of a particularly preferable model of FIG. 1and/or of the device described in the previous examples. The numberingcorresponds to FIG. 1.

We claim:
 1. A device for the performance of urease tests on combinedantrum/corpus biopsies which are placed in substratum for carrying outdiagnoses of gastrointestinal disorders, comprising:a) a carrier platewith a field thereon for marking patient identification and clinicaldata; b) a schematic representation of the stomach on the carrier plate;c) at least one opening in the carrier plate in the region on theschematic representation corresponding to the corpus, and at least oneopening to the carrier plate in the region on the representationcorresponding to the antrum; d) an evaluation scale provided on saidcarrier plate for the assessment of the urease tests; e) wherein said atleast one opening in the carrier plate in the region on the schematicrepresentation corresponding to the corpus and said at least one openingin the carrier plate in the region on the schematic representationcorresponding to the antrum each include at least one container attachedto the carrier plate for holding substratum for the urease tests, eachsaid container having an opening for receiving corpus/antrum biopsiestherein.
 2. The device of claim 1, further including a cover for eachcontainer opening.
 3. The device of claim 2, wherein said cover isprovided with an adhesive seal.
 4. The device of claim 3, wherein theschematic representation of the stomach is provided on the adhesiveseal.
 5. The device of claim 2, wherein the container has a rim whichprotrudes outwardly from the carrier plate.
 6. The device of any one ofclaims 2 or 5, wherein the cover is provided with a screw-type closureincluding a cylindrical insert which presses a biopsy to be collectedinto the substratum.
 7. The device of any one of claims 1, 2 or 5,wherein the schematic representation of the stomach is engraved into thecarrier plate.
 8. The device of claim 1, wherein the substratum for theurease test comprises a gel-type form having a pH value of from about5.9 to 6.1, with the substratum containing, in amounts per 1000 g: 0.1 gyeast extract, 0.1 g potassium dihydrogen phosphate, 0.6 g phenol red,14.4 g agar, 0.1 g dextrose, 19.2 g carbamide, 2.9 ml vitamin solution,and 0.1 ml trace elements.
 9. The device of claim 8, wherein the vitaminsolution referred to is prepared by dissolving 0.198 g D (+) vitamin H,1.977 g niacin, 0.988 g vitamin B₁, 0.988 g para aminobenezynecarboxylic acid, 0.494 g deuterium pantothenic acid-sodium salt, 4.942 gof Pyridoxamine dihydrochloride, and 1.977 g vitamin B₁₂ in 988.435 g ofdistilled water with sterile filtration following; and wherein thesolution of trace elements referred to is prepared by dissolving 0.049 gof barium chloride.2 H₂ O, 0.198 g neutral potassium iodide, 0.198 gpotassium bromide, 0.099 g boric acid, 0.049 g tin chloride, 0.049 glithium chloride, 0.198 g zinc chloride.2 H₂ O, 0.099 g copper (II)sulfate.5 H₂ O, 0.198 g cobalt chloride.6 H₂ O, 0.099 g manganesedichloride.4 H₂ O, 7.919 g N,N'-1,2-ethanediyl-bisN-(carboxymethyl)glycine!disodium salt.2 H₂ O, 0.01 g iron (II)sulfate.7 H₂ O, and 0.099 g sodium molybdate.H₂ O in 989.844 g distilledwater.